AJP - Endocrinology and Metabolism, Vol 270, Issue 2 E209-E214, Copyright © 1996 by American Physiological Society

ARTICLES

Plasma methionine and cysteine kinetics in response to an intravenous glutathione infusion in adult humans

N. K. Fukagawa, A. M. Ajami and V. R. Young
Clinical Research Center, Rockefeller University, New York, New York 10021, USA.

Glutathione (GSH), a tripeptide (gamma-glutamyl-cysteinyl-glycine), is thought to be both a storage and a transport form of cysteine (Cys). In a previous study (T. Hiramatsu, N.K. Fukagawa, J.S. Marchini, J. Cortiella, Y.-M. Yu, T.E. Chapman, and V.R. Young. Am. J. Clin. Nutr. 60: 525-533, 1994), the direct tracer-derived estimate of Cys flux was considerably higher than that predicted from estimates of protein turnover. To further examine the components of plasma Cys flux, seven normal-weight healthy adult men and women (26 +/- 2 yr) received stable isotope tracer infusions of L-[methyl-2H3;1-13C]methionine, L-[3,3-2H2]cysteine, and L-[methyl-2H3]leucine for 460 min. After a 3-h baseline period, GSH was administered at approximately 32 mumol.kg-1.h-1 until the end of the study. Expired breath and blood samples were obtained at timed intervals and analyzed for isotope enrichment using mass spectrometry. Leucine, alpha-ketoisocaproate, and methionine (carboxyl carbon, methyl moiety, remethylation, and transsulfuration) turnover were reduced during GSH administration (P < 0.01). In the final hour of GSH administration, Cys flux increased by 61% from 55.1 +/- 1.7 to 88.7 +/- 5.2 mumol.kg-1.h-1 (P < 0.01), which was essentially equivalent to the rate of exogenous GSH infusion. These data suggest that GSH breakdown accounts for approximately 50% of tracer-derived Cys flux basally and for all of the increase in measured Cys turnover during exogenous GSH infusion.

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